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In hepatocytes and alcohol-metabolizing cultured cells, Golgi undergoes ethanol (EtOH)-induced disorganization. Perinuclear and organized Golgi is important in liver homeostasis, but how the Golgi remains intact is unknown. Work from our laboratories showed that EtOH-altered cellular function could be reversed after alcohol removal; we wanted to determine whether this recovery would apply to Golgi. We used alcohol-metabolizing HepG2 (VA-13) cells (cultured with or without EtOH for 72 h) and rat hepatocytes (control and EtOH-fed (Lieber⁻DeCarli diet)). For recovery, EtOH was removed and replenished with control medium (48 h for VA-13 cells) or control diet (10 days for rats). Results: EtOH-induced Golgi disassembly was associated with de-dimerization of the largest Golgi matrix protein giantin, along with impaired transport of selected hepatic proteins. After recovery from EtOH, Golgi regained their compact structure, and alterations in giantin and protein transport were restored. In VA-13 cells, when we knocked down giantin, Rab6a GTPase or non-muscle myosin IIB, minimal changes were observed in control conditions, but post-EtOH recovery was impaired. Conclusions: These data provide a link between Golgi organization and plasma membrane protein expression and identify several proteins whose expression is important to maintain Golgi structure during the recovery phase after EtOH administration.

Exosomes participate in cell-to-cell communication, facilitated by the transfer of RNAs, proteins and lipids from donor to recipient cells. Exosomes and their RNA cargos do not exclusively originate from endogenous synthesis but may also be obtained from dietary sources such as the inter-species transfer of exosomes and RNAs in bovine milk to humans. Here, we assessed the bioavailability and distribution of exosomes and their microRNA cargos from bovine, porcine and murine milk within and across species boundaries. Milk exosomes labeled with fluorophores or fluorescent fusion proteins accumulated in liver, spleen and brain following suckling, oral gavage and intravenous administration in mice and pigs. When synthetic, fluorophore-labeled microRNAs were transfected into bovine milk exosomes and administered to mice, distinct species of microRNAs demonstrated unique distribution profiles and accumulated in intestinal mucosa, spleen, liver, heart or brain. Administration of bovine milk exosomes failed to rescue Drosha homozygous knockout mice, presumably due to low bioavailability or lack of essential microRNAs.

Activating KIR-HLA-C ligand complexes and HLA-G∗14bp insertion/deletion (+/-) polymorphism were associated to Autism Spectrum Disorders (ASD) and were suggested to correlate with inflammation during fetal development. We evaluated whether HLA-G∗14bp(+/-) and KIR-HLA-C complexes are associated with cognitive and behavioral scores and EEG profile in 119 ASD children (58 from Sardinia, 61 from Peninsular Italy). KIR2DS1-C2; KIR2DS2-C1; KIR2DL1-C2; KIR2DL2-C1; KIR2DL3-C1 and HLA-G∗14bp(+/-) were molecularly genotyped by Single Specific Primer PCR and gel electrophoresis. Univariate linear model analysis adjusted for age, gender and provenience showed statistically higher scores of Childhood Autism Rating Scale (CARS) and Autistic Core Behavior in KIR2DS1-C2+/HLA-G∗14bp+ASD children (43.7±1.5, p=0.03; 3.3±0.1, p=0.03, respectively). These results suggested a synergistic polygenic association of KIR2DS1-HLAC2+/HLA-G∗14bp+ pattern with behavioral impairment in ASD children., (Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.)

This paper presents a novel strategy aiming to acquire an accurate and walking-speed-adaptive estimation of the gait phase through noncontact capacitive sensing and adaptive oscillators (AOs). The capacitive sensing system is designed with two sensing cuffs that can measure the leg muscle shape changes during walking. The system can be dressed above the clothes and free human skin from contacting to electrodes. In order to track the capacitance signals, the gait phase estimator is designed based on the AO dynamic system due to its ability of synchronizing with quasi-periodic signals. After the implementation of the whole system, we first evaluated the offline estimation performance by experiments with 12 healthy subjects walking on a treadmill with changing speeds. The strategy achieved an accurate and consistent gait phase estimation with only one channel of capacitance signal. The average root-mean-square errors in one stride were 0.19 rad (3.0% of one gait cycle) for constant walking speeds and 0.31 rad (4.9% of one gait cycle) for speed transitions even after the subjects rewore the sensing cuffs. We then validated our strategy in a real-time gait phase estimation task with three subjects walking with changing speeds. Our study indicates that the strategy based on capacitive sensing and AOs is a promising alternative for the control of exoskeleton/orthosis.

Desmoplastic small round cell tumor of the pleura is a rare malignancy, with only a few cases reported in the scientific literature. The aim of the present review is to discuss the demographic, pathological, clinical, and therapeutic features of this rare tumor. English-language articles published since 1989, when the first case of desmoplastic small round cell tumor of the pleura was described, were retrieved, and fifteen cases included in fourteen articles were revised. The mean age of the patients was 25.5 years, out of them 60% were males. Chest pain, pleural effusion, and dyspnea were the most common clinical manifestations, while chest roentgenogram and computed tomography were the imaging techniques most commonly used. Surgical biopsy was employed in 80% of the cases for diagnosis. A multidisciplinary approach consisting in a combination of surgery with chemotherapy and radiation therapy was adopted in most cases. Only two patients (13.3%) were alive at 3 years from diagnosis, reflecting the aggressiveness of the disease, and the poor outcomes of the treatments currently available. Desmoplastic small round cell tumors of the pleura are extremely aggressive and challenging to diagnose, because of their rarity and unspecific demographic, clinical, and radiological features. An in-depth knowledge of such features is necessary for the optimal management of patients with this rare malignancy.

Extracellular vesicles (EVs) in milk harbor a variety of compounds, including lipids, proteins, noncoding RNAs, and mRNAs. Among the various classes of EVs, exosomes are of particular interest, because cargo sorting in exosomes is a regulated, nonrandom process and exosomes play essential roles in cell-to-cell communication. Encapsulation in exosomes confers protection against enzymatic and nonenzymatic degradation of cargos and provides a pathway for cellular uptake of cargos by endocytosis of exosomes. Compelling evidence suggests that exosomes in bovine milk are transported by intestinal cells, vascular endothelial cells, and macrophages in human and rodent cell cultures, and bovine-milk exosomes are delivered to peripheral tissues in mice. Evidence also suggests that cargos in bovine-milk exosomes, in particular RNAs, are delivered to circulating immune cells in humans. Some microRNAs and mRNAs in bovine-milk exosomes may regulate the expression of human genes and be translated into protein, respectively. Some exosome cargos are quantitatively minor in the diet compared with endogenous synthesis. However, noncanonical pathways have been identified through which low concentrations of dietary microRNAs may alter gene expression, such as the accumulation of exosomes in the immune cell microenvironment and the binding of microRNAs to Toll-like receptors. Phenotypes observed in infant-feeding studies include higher Mental Developmental Index, Psychomotor Development Index, and Preschool Language Scale-3 scores in breastfed infants than in those fed various formulas. In mice, supplementation with plant-derived MIR-2911 improved the antiviral response compared with controls. Porcine-milk exosomes promote the proliferation of intestinal cells in mice. This article discusses the above-mentioned advances in research concerning milk exosomes and their cargos in human nutrition. Implications for infant nutrition are emphasized, where permitted, but data in infants are limited., Competing Interests: 2 Author disclosures: J Zempleni, A Aguilar-Lozano, M Sadri, S Sukreet, S Manca, D Wu, F Zhou, and E Mutai, no conflicts of interest., (© 2017 American Society for Nutrition.)

The purpose of this study was to analyse the effects of residential facilities' design features on older adults' psychosocial responses. Participants ( N  = 192) were over 65-year-old residents who were randomly exposed to different experimental scenarios concerning a hypothetical residential facility for older adults, using a 3 × 2 between-subjects design (i.e. home-like vs. hotel-like vs. usual-standard architectural style; presence vs. absence of green spaces). After the experimental session, participants were asked to fill in a questionnaire that measured their attitudes towards short- and long-term relocation, anticipated residential satisfaction with the facility, and feelings of broken home attachment. The results showed (1) more positive responses to "home-like" and "hotel-like" architectural styles than the usual-standard type and (2) the positive impact of green spaces on the assessment of the facilities. These design features should thus play a role in both reducing the stressful impact of leaving home and promoting beneficial patterns, hence fostering "successful ageing".

Encapsulation of microRNAs in exosomes confers protection against degradation and a vehicle for shuttling of microRNAs between cells and tissues, and cellular uptake by endocytosis. Exosomes can be found in foods including milk. Humans absorb cow's milk exosomes and deliver the microRNA cargo to peripheral tissues, consistent with gene regulation by dietary nucleic acids across species boundaries. Here, we tested the hypothesis that human vascular endothelial cells transport milk exosomes by endocytosis, constituting a step crucial for the delivery of dietary exosomes and their cargo to peripheral tissues. We tested this hypothesis by using human umbilical vein endothelial cells and fluorophore-labeled exosomes isolated from cow's milk. Exosome uptake followed Michaelis-Menten kinetics (Vmax = 0.057 ± 0.004 ng exosome protein × 40,000 cells/h; Km = 17.97 ± 3.84 μg exosomal protein/200 μl media) and decreased by 80% when the incubation temperature was lowered from 37°C to 4°C. When exosome surface proteins were removed by treatment with proteinase K, or transport was measured in the presence of the carbohydrate competitor d-galactose or measured in the presence of excess unlabeled exosomes, transport rates decreased by 45% to 80% compared with controls. Treatment with an inhibitor of endocytosis, cytochalasin D, caused a 50% decrease in transport. When fluorophore-labeled exosomes were administered retro-orbitally, exosomes accumulated in liver, spleen, and lungs in mice. We conclude that human vascular endothelial cells transport bovine exosomes by endocytosis and propose that this is an important step in the delivery of dietary exosomes and their cargo to peripheral tissues., (Copyright © 2016 the American Physiological Society.)

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Several authors report MS affecting not only young adults but also children and adolescents. Sardinia is one of the regions at the highest risk for MS worldwide in the adult population; to date, no definite data exist on the pediatric population. The aim of this study was to estimate the incidence and prevalence of pediatric MS (pMS) in northern Sardinia. Patients with diagnosis of optic neuritis, myelitis, acute disseminated encephalomyelitis (ADEM), demyelinating disorders, MS, or clinically isolated syndrome (CIS) according to McDonald criteria were enrolled, when disease onset occurred within the range of 0-18 years. From January 1, 2001 to December 31, 2012, 21 cases of pMS and 5 cases of CIS were found in northern Sardinia. The annual mean pMS incidence was 2.85 cases per 100,000 pediatric population, and the annual mean CIS incidence was 0.68 cases per 100,000 pediatric population. The pMS and CIS prevalence computed on 31 December 2012 was 26.92 and 6.41 per 100,000 pediatric population, respectively., Conclusion: Our pMS data among Sardinians corroborate the epidemiological scenario described in the adult population being the incidence estimates significantly higher than those reported elsewhere., What Is Known: Sardinia is one of the regions at the highest risk for MS worldwide in the adult population. To date, no definite data exist on the pediatric population., What Is New: The pediatric MS incidence in Sardinia is estimated to be significantly higher than those reported elsewhere. The pediatric MS prevalence in Sardinia is among the highest values worldwide.

Studies conducted in the 1980s (see Canter et al. in Football in its place. An environmental psychology of football grounds. Routledge, London, 1989) highlighted the prominent role of the spatial-physical features of football grounds in influencing users' perception of safety, comfort, and general satisfaction towards the stadium experience. In particular, the importance of fulfilling the spectators' needs of personal space (e.g. presence of an open view, proper distance between the seats) and movement opportunity was analysed. The aim of this study is to confirm the factorial structure of a set of indicators--the IPEQS--concerning the perceived quality of an array of aspects (i.e. architectural, social, functional, and safety issues) related to the stadium design. Participants (N = 255), who were selected on the basis of their stadium experience, filled in a self-report questionnaire measuring a set of indicators developed on the basis of both validated tools [i.e. the perceived residential environment quality indicators (PREQIs): Bonaiuto et al. in J Environ Psychol 19:331-352, 1999] and outcomes of semi-structured interviews. Confirmatory factor analyses (CFA) were performed for each scale, and reliability assessments were then carried out for each indicator. IPEQS' factorial structures found through the CFA procedure substantially confirm the results of exploratory factor analyses run with previous data. Outcomes of this study should provide a useful tool for managers and designers of football grounds, in order to improve the overall experience of the spectators.

This paper concerns people's assessment of their neighborhood of residence in a Chinese urban context. The aim of the study was to verify the factorial structure and the reliability of two instruments originally developed and validated in Italy (the full versions of the Perceived Residential Environment Quality Indicators [PREQIs] and of the Neighborhood Attachment Scale [NAS]) in a different cultural and linguistic context. The instruments consist of 11 scales measuring the PREQIs and one scale measuring neighborhood attachment (NA). The PREQIs scales include items covering four macroevaluative domains of residential environment quality: architectural and urban planning aspects (three scales: Architectural and Town-planning Space, Organization of Accessibility and Roads, Green Areas), sociorelational aspects (one scale: People and Social Relations), functional aspects (four scales: Welfare Services, Recreational Services, Commercial Services, and Transport Services), and contextual aspects (three scales: Pace of Life, Environmental Health, Upkeep and Care). The PREQIs and NAS were included in a self-report questionnaire, which had been translated and back-translated from English to Chinese, and was then administered to 340 residents in six districts (differing along various features) of a highly urbanized context in China, the city of Chongqing. Results confirmed the factorial structure of the scales and demonstrated good internal consistency of the indicators, thus reaffirming the results of previous studies carried out in Western urban contexts. The indicators tapping the neighborhood's contextual aspects (i.e., pace of life, environmental health, and upkeep) emerged as most correlated to NA., (© 2015 The Institute of Psychology, Chinese Academy of Sciences and Wiley Publishing Asia Pty Ltd.)

Background: Pulmonary tuberculosis (TB), a highly contagious infectious disease, is a significant public health problem all over the world and remains an important cause of preventable death in the adult population. Endobronchial TB is an unusual form of thoracic TB that may be complicated by tracheobronchial stenosis, and bronchoesophageal fistula formation is a very rare complication. Tubercular lymphadenitis can also lead to fistula formation through a process of caseum necrosis and opening of a fistula between the bronchus and oesophagus., Case Report: We report an uncommon case of thoracic TB in an immunocompetent 73-year-old Caucasian man who presented several problems: bronchoesophageal fistula, endobronchial TB, and mediastinal lymphadenopathy in the absence of contemporary parenchymal consolidation. Furthermore, he presented a normal chest radiograph and mostly unclear and non-specific symptoms at onset., Conclusions: We emphasize the need for a better knowledge of this illness and awareness that it may have an unusual presentation. In these cases, diagnosis and proper treatment can be delayed, with severe complications for the patient. Pulmonary TB remains a real diagnostic challenge: a normal chest radiograph and nonspecific symptoms do not allow us to exclude this persistent infectious disease.

In the framework of the INSuLa project, supported by Italian Ministry of Health, a national survey was conducted to evaluate the perceptions of employers about Occupational Safety and Health (OSH) activities. Main findings of this survey are presented in this paper. The survey was conducted on a sample of 1,010 employers weighted by economic activity sector, company size and geographic area. An ad hoc questionnaire was administered through Computer Assisted Telephone Interviewing methodology. Most of employers "mostly" or "completely" agree with the usefulness of OSH activities and the efficacy of specific prevention and protection measures. Around 37.7% of employers consider OSH management a shared responsibility with workers and 56.1% of them feel the OSH level to be increased following the implementation of Legislative Decree no. 81/08. The findings of this survey provide a picture of Italian employers' point of view about OSH and identify gaps and needs, thus contributing to choose proper actions for the improvement of OSH

Alpha-1-antitrypsin deficiency (AATD) is an inherited disorder responsible for early onset emphysema associated with a significant impairment of health-related quality of life (HRQoL). Our aim was to assess the usefulness of different instruments to evaluate the HRQoL in patients with AATD compared to non-AATD COPD. Observational, cross-sectional study in which all patients filled out a series of questionnaires: the COPD severity score (COPDSS), the EuroQoL 5-Dimensions (EQ-5D), the Living with COPD (LCOPD) and the COPD Assessment Test (CAT). A total of 96 patients were included, 35 with AATD (mean age 56.5 yrs, 57.1% male and mean FEV1(%) 48.7% and 61 non-AATD COPD (70.3 yrs, 80.3% men and FEV1(%) 47%. The questionnaire scores were similar, with a tendency towards worse scores in AATD for the EQ-5D (VAS) (64.8 (20.2) vs. 71.6 (17.1); p = 0.08). The correlations between the different scores and FEV1(%) were significant in both groups for COPDSS and LCOPD, but not for CAT and EQ-5D. In general, the correlations of scores with FEV1(%) were stronger for AATD compared with non-AATD COPD patients: COPDSS r = -0.570, p < 0.01 for AATD and r = -0.260, p < 0.05 for COPD; LCOPD r = -0.502, p < 0.001 for AATD and r = -0.304, p < 0.05 for non-AATD COPD. Patients with AATD have a similar degree of HRQoL impairment as older subjects with non-AATD COPD and showed a stronger correlation between HRQoL measurements and lung function impairment compared with non-AATD COPD. This may be related to the characteristics of the disease in these patients who are usually younger, with less co-morbidity and lower smoking consumption.

Within the complex pathological picture associated to diabetes, high glucose (HG) has "per se" effects on cells and tissues that involve epigenetic reprogramming of gene expression. In fetal tissues, epigenetic changes occur genome-wide and are believed to induce specific long term effects. Human umbilical vein endothelial cells (HUVEC) obtained at delivery from gestational diabetic women were used to study the transcriptomic effects of chronic hyperglycemia in fetal vascular cells using Affymetrix microarrays. In spite of the small number of samples analyzed (n=6), genes related to insulin sensing and extracellular matrix reorganization were found significantly affected by HG. Quantitative PCR analysis of gene promoters identified a significant differential DNA methylation in TGFB2. Use of Ea.hy926 endothelial cells confirms data on HUVEC. Our study corroborates recent evidences suggesting that epigenetic reprogramming of gene expression occurs with persistent HG and provides a background for future investigations addressing genomic consequences of chronic HG., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The activity of natural killer (NK) cells is modulated by the interaction between killer-cell immune globulin-like receptor (KIR) proteins and their cognate HLA ligands; activated NK cells produce inflammatory cytokines and mediate innate immune responses. Activating KIR/HLA complexes (aKIR/HLA) were recently suggested to prevail in children with autism spectrum disorders (ASD), a neurodevelopmental syndrome characterized by brain and behavioral abnormalities and associated with a degree of inflammation. We verified whether such findings could be confirmed by analyzing two sample cohorts of Sardinian and continental Italian ASD children and their mothers. Results showed that aKIR/HLA are increased whereas inhibitory KIR/HLA complexes are reduced in ASD children; notably this skewing was even more significant in their mothers. KIR and HLA molecules are expressed by placental cells and by the trophoblast and their interactions result in immune activation and influence fetal, as well as central nervous system development and plasticity. Data herein suggest that in utero KIR/HLA immune interactions favor immune activation in ASD; this may play a role in the pathogenesis of the disease., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Notch signaling plays a complex role in carcinogenesis, and its signaling pathway has both tumor-suppressor and oncogenic components. In this study we investigated the effects of reactive oxygen species (ROS) on Notch1 signaling outcome in keratinocyte biology. We demonstrate that Notch1 function contributes to the arsenic-induced keratinocyte transformation. We found that acute exposure to arsenite increases oxidative stress and inhibits proliferation of keratinocyte cells by upregulation of p21(waf1/Cip1). The necessity of p21(waf1/Cip1) for arsenite-induced cell death was demonstrated by targeted downregulation of p21(waf1/Cip1) by using RNA interference. We further demonstrated that on acute exposure to arsenite, p21(waf1/Cip1) is upregulated and Notch1 downmodulated, whereas on chronic exposure to arsenite, malignant progression of arsenite-treated keratinocytes cells was accompanied by regained expression and activity of Notch1. Notch1 activity in arsenite-transformed keratinocytes inhibits arsenite-induced upregulation of p21(waf1/Cip1) by sustaining c-myc expression. We further demonstrated that c-myc collaborates with Nrf2, a key regulator for the maintenance of redox homeostasis, to promote metabolic activities that support cell proliferation and cytoprotection. Therefore, Notch1-mediated repression of p21(waf1/Cip1) expression results in the inhibition of cell death and keratinocytes transformation. Our results not only demonstrate that sustained Notch1 expression is at least one key event implicated in the arsenite human skin carcinogenic effect, but also may provide mechanistic insights into the molecular aspects that determine whether Notch signaling will be either oncogenic or tumor suppressive.

Background and Purpose: A large number of subjective experiences and beliefs with some degree of affinity with psychotic symptoms can be found in the general population. However, the appraisal of these psychotic-like experiences in terms of associated distress, raised preoccupation, and the conviction with which the experience is held can be more discriminative in distinguishing people in need for care from those who simply hold unusual or uncommon beliefs because of cultural reasons., Method: In this study, 81 patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of schizophrenia or an affective disorder with psychotic features were compared on the Peters et al Delusions Inventory (PDI) to 210 people from the same local area, who had never received a formal diagnosis of a mental disorder., Results: Patients scored higher than controls on the PDI total score and on its distress, preoccupation, and conviction subscales. A stepwise logistic regression model showed PDI-preoccupation (odds ratio, 2.46; 95% confidence interval, 1.52-3.98) and, marginally, PDI-distress (odds ratio = 1.58; 95% confidence interval, 0.93-2.58) adding discriminative power to PDI total score in distinguishing patients from controls., Conclusions: The evaluation of the severity of delusion-like experiences and beliefs is important in discriminating patients diagnosed with psychosis from people who are not in need of care., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Hailey-Hailey disease (HHD) is an autosomal dominant disorder characterized by suprabasal cutaneous cell separation (acantholysis) leading to the development of erosive and oozing skin lesion. Micro RNAs (miRNAs) are endogenous post-transcriptional modulators of gene expression with critical functions in health and disease. Here, we evaluated whether the expression of specific miRNAs may play a role in the pathogenesis of HHD. Here, we report that miRNAs are expressed in a non-random manner in Hailey-Hailey patients. miR-125b appeared a promising candidate for playing a role in HHD manifestation. Both Notch1 and p63 are part of a regulatory signalling whose function is essential for the control of keratinocyte proliferation and differentiation and of note, the expression of both Notch1 and p63 is downregulated in HHD-derived keratinocytes. We found that both Notch1 and p63 expression is strongly suppressed by miR-125b expression. Additionally, we found that miR-125b expression is increased by an oxidative stress-dependent mechanism. Our data suggest that oxidative stress-mediated induction of miR-125b plays a specific role in the pathogenesis of HHD by regulating the expression of factors playing an important role in keratinocyte proliferation and differentiation., (© 2011 John Wiley & Sons A/S.)

Synaptosomal-associated protein of 25kD (SNAP-25), a protein participating in the regulation of synaptic vesicle exocytosis and in calcium homeostasis, was recently involved in neuropsychiatric conditions. Because alterations affecting the homeostasis of calcium are described in patients affected by autism spectrum disorders (ASD) we investigated a possible involvement of SNAP-25 in ASD by evaluating five SNAP-25 gene polymorphisms in a cohort of 67 ASD children. Data analyzed in relationship with clinical outcomes and compared to those of 205 healthy sex-matched children did not reveal significant differences. Further analyses nevertheless showed the presence of highly significant associations of the rs363043 (CT) genotype, localized in the intron 1 region that affects the transcription factor binding sites of the SNAP-25 gene, with both increasing CARS (p=0.001) and hyperactivity scores (p=0.006). The finding that polymorphisms of the SNAP-25 gene, a gene involved in neurotransmission and regulation of calcium homeostasis, are associated with the degree of hyperactivity in children with ASD, reinforces the hypothesis that alterations of these mechanisms play a pivotal role in the events leading to ASD-associated behavioral impairment. Modulation of these processes could result in novel therapeutic strategies., (2011 Elsevier Ltd. All rights reserved.)

To verify correlations between HLA and autism spectrum disorders (ASD) we studied 61 Italian families with an ASD child; results showed such correlation in 65% of cases. Case-control and TDT analysis of intrafamilial transmission of SNPs, Msats, and HLA markers surrounding the α and β blocks, indicated significant positive associations for MOGc*131 and D6S2239*105 alleles in ASD, and a negative association of MIB *332 allele in healthy siblings. Polymorphism haplotype analysis demonstrated that two haplotypes comprising the TNF-238(G)-TNF-308(G)-MIB*332-HLA-B*38-HLA-Cw*12 and the D6S265*218-HLA-A*23-MOGc*131-rs2857766(G) alleles are more frequently transmitted to ASD. MOGc and MIB loci are linked with ASD in Italian patients., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Synaptosomal-associated protein of 25 KD (SNAP-25) is a protein that participates in synaptic vesicle exocytosis through the formation of a SNARE complex; SNAP-25 also plays a pivotal role in modulating calcium homeostasis through negative regulation of voltage-gated calcium channels. SNAP-25 has been involved in different neuropsychiatric disorders, including attention deficit hyperactivity disorder. There are well known physiological gender differences in many neuropsychological skills, and there are even more striking gender differences in patients with attention deficit hyperactivity disorder and autism spectrum disorders. We hypothesize that these differences are the result of a mechanism involving SNAP-25 polymorphisms and its differential expression in specific brain areas.

Analyses of a 6-Mb region spanning the human leukocyte antigen (HLA) region from the HLA-DR to the HFE gene were performed in 37 families of Sardinian ancestry, all of whom had at least one autistic child, to identify genetic markers associated with autism spectrum disorders (ASD) development. In particular, four microsatellites (MIB, D6S265, MOGc, and D6S2239) and three single-nucleotide polymorphisms (SNPs; two in positions -308 and -238 in the promoter of the TNF-alpha and SNP rs2857766 [V142L] in exon 3 of the MOG gene) were analyzed. An intrafamilial case-control method (affected family-based controls) and transmission disequilibrium test analysis were used to evaluate the association of microsatellite and SNP markers with ASD-affected children. Results indicated positive associations with ASD for D6S265*220 (p < 0.01) and MOGc*131 (p < 0.05) and negative associations for MOGc*117 and MIB*346 alleles (p < 0.01) in ASD children. Polymorphism haplotype analysis indicated that D6S265 allele *220 and MOGc allele *131 were significantly more likely to be transmitted together, as a whole haplotype, to ASD children (p < 0.05). Conversely, the D6S265*224-MOGc*117-rs2857766(G) haplotype was significantly less frequently transmitted to ASD children (p < 0.01). The results present novel gene markers, reinforcing the hypothesis that genetic factors play a pivotal role in the pathogenesis of ASD.

We propose a new capillary zone electrophoresis method applying short-end injection technique for the fast evaluation of methylcystosine/total cytosine ratio after acidic DNA hydrolysis. By short-end injection and by using a 100 mmol/l Tris solution titrated with 1 mol/l phosphoric acid to pH 3.75 as background electrolyte, cytosine and methylcytosine were separated with a good resolution in less than 1.5 min. Stepwise multiple linear regression with DNA methylation degree as the dependent variable and age, cysteine, homocysteine and methionine as independent variables, showed a negative association with age and that total cysteine is the most important determinant of DNA methylation.

Objective: To establish sensitivity, specificity, and discriminative validity of the Peters et al Delusions Inventory (PDI), a recently released self-compiled questionnaire aimed at measuring psychosis proneness in the general population., Method: Eighty-one patients diagnosed with a mental disorder with psychotic features (schizophrenia, schizoaffective disorder, bipolar disorder, major depression) and 210 putatively healthy individuals were invited to complete the PDI and the brief version of the General Health Questionnaire (GHQ-12). The receiver operating characteristic analysis has been used to extract the best threshold to discriminate between cases, those with a psychotic disorder, and noncases, those without a psychotic disorder., Results: The best PDI threshold in discriminating between cases and noncases was 8 (sensitivity, 74%; specificity, 79%). The corresponding figures of sensitivity and specificity for a GHQ-12 cutoff of 6 were 63% and 83%, respectively. The value of the area under the receiver operating characteristic curve was found to be higher for the PDI (0.815) than for the GHQ-12 (0.770), although at a barely detectable, statistically significant difference (Z = 1.45, P = .073)., Conclusion: The expected high negative predictive value of the PDI (96%) in the general population suggests it will be a valuable tool in future research on psychosis proneness.

We have recently demonstrated that low-density lipoprotein (LDL) apoprotein is able to bind the most concentrated plasma thiols such as cysteine, cysteinylglycine, and homocysteine by disulfide linkage. However, the LIF CE assay employed to measure linked thiols was not sensitive enough to verify whether low concentrated plasma thiols as glutathione and glutamylcysteine are also linked to apoprotein. By modifying sample treatment and electrophoretic parameters we set up a new method with an LOQ of about 1.5 nmol/L, by which we demonstrate that LDL apoprotein binds all physiological plasma thiols. The increased sensitivity was obtained by drying released apoB thiols after reduction treatment, dissolving them directly in a low volume of derivatization buffer and decreasing the dilution factor of derivatized sample before CE injection. Moreover, by increasing the concentration of the electrolyte buffer, we improved the selectivity of peaks, in particular between glutathione (GSH) and the impurity peak derived from unreacted 5-iodoacetamidofluorescein, which in the previous electrophoretic conditions were overlapped. The method optimization, reached by searching the best combination between sample matrix and CE run buffer, is fully described. Given the potential pathologic significance of protein thiolation, the proposed method may be useful to understand the mechanisms and the balances that regulate the interaction between thiols and -SH free groups of proteins.

Autism spectrum disorders (ASD) are characterized by a broad range in clinical presentation. Although a definite genetic cause has not yet been fully demonstrated, family based studies suggest that a multigenic pattern may be responsible for susceptibility, but most results are conflicting and have yet to be replicated. The purpose of this investigation was to analyze the linkage of the human leukocyte antigen (HLA) and the human serotonin transporter coding (5-HTTLPR) genes with ASD in a group of 37 families of Sardinian ethnicity in insular Italy. In 50% of these families, ASD is linked to HLA, and in the other 50% it is linked to 5-HTTLPR polymorphic genes; in other words, linkage to one or the other was evident in all cases. Despite a very homogenous genetic pattern being generally reported for Sardinians, the linkage observed with HLA and 5-HTTLPR genetic regions indicated a statistically defined heterogeneity (p=0.002). No allelic HLA or 5-HTTLPR polymorphisms were specifically associated with ASD, suggesting these loci as markers of other genes mapped in their close proximity that may be more directly involved and thus may merit further analytical studies.

Objective: To evaluate the clinical and radiological response of chronic calcific tendinitis of the shoulder to extracorporeal shock wave therapy (ESWT) in a single blind study., Methods: 70 patients showing chronic, symptomatic, calcifying tendinitis of the shoulder were examined. A single blind randomised study was performed with 35 patients undergoing a regular treatment (group 1) and 35 a simulated one (group 2). Pain and functional assessment was carried out according to Constant and Murley. Variations in the dimension of the calcification were evaluated by anteroposterior x ray films., Results: A significant decrease of pain and a significant increase in shoulder function was seen in group 1. Examination by x ray showed partial resorption of the calcium deposits in 40% of cases and complete resorption in 31% of cases in group 1. In the control group no significant decrease of pain and no significant increase in shoulder function was seen. No modifications were observed by x ray examination., Conclusion: Because of its good tolerance, safety, and clinical radiological response, ESWT can be considered as an alternative treatment for chronic calcific tendinitis of the shoulder.

Objective: To evaluate the efficacy of extracorporeal shock wave treatment (ESWT) in calcaneal enthesophytosis., Methods: 60 patients (43 women, 17 men) were examined who had talalgia associated with heel spur. A single blind randomised study was performed in which 30 patients underwent a regular treatment (group 1) and 30 a simulated one (shocks of 0 mJ/mm(2) energy were applied) (group 2). Variations in symptoms were evaluated by visual analogue scale (VAS). Variations in the dimension of enthesophytosis were evaluated by x ray examination. Variations in the grade of enthesitis were evaluated by sonography., Results: A significant decrease of VAS was seen in group 1. Examination by x ray showed morphological modifications (reduction of the larger diameter >1 mm) of the enthesophytosis in nine (30%) patients. Sonography did not show significant changes in the grade of enthesitis just after the end of the treatment, but a significant reduction was seen after one month. In the control group no significant decrease of VAS was seen. No modification was observed by x ray examination or sonography., Conclusion: ESWT is safe and improves the symptoms of most patients with a painful heel, it can also structurally modify enthesophytosis, and reduce inflammatory oedema.

We describe a large family from Sardinia, Italy, in which a novel X- linked mental retardation (XLMR) syndrome segregates. The phenotype observed in the 8 affected males includes severe mental retardation (MR), lack of speech, coarse face, distinctive skeletal features with short stature, brachydactyly of fingers and toes, small downslanting palpebral fissures, large bulbous nose, hypoplastic ear lobe and macrostomia. Carrier females are not mentally retarded, although some of them have mild dysmorphic features such as minor ear lobe abnormalities, as well as language and learning problems. Linkage analysis for X-chromosome markers resulted in a maximum lod score of 3.61 with marker DXS1001 in Xq24. Recombination observed with flanking markers identified a region of 16 cM for further study. None of the other XLMR syndromes known to map in the same region shows the same composite phenotype. This evidence strongly suggests that the genetic disease in this family is unique.

This study assessed the analgesic action of tramadol compared with placebo in patients suffering from fibromyalgia syndrome. Twelve patients (11 females, one male) were treated according to a double-blind crossover experimental design. Each patient, after signing informed consent, was randomly allocated to either tramadol (100 mg ampul in 100 ml given intravenously in 15 min doses) or placebo for a single dose treatment. At the second visit, patients crossed over to the other drug for a further single dose treatment. There was a wash-out period of 1 week. Nine patients completed the study, while in three cases (two tramadol, one placebo) the study was discontinued due to the onset of side effects. The assessment of efficacy, carried out at the baseline and 15 min and 2 hours after administration of each dose, involved the use of a visual analog scale (VAS 100 mm) for spontaneous pain and pressure dolorimetry (kg/cm2) at 12 "symptomatic" tender points and nine "control" tender points for fibromyalgic pain. During the first treatment cycle effective control of spontaneous pain was achieved with tramadol, which determined a reduction of 20.6% while with the placebo spontaneous pain increased by 19.8%. With pressure dolorimetry there were no clinically important differences observed after either active treatment or placebo. The contrasting results found in the present study could be a stimulus for the organization of new projects, which may lead to the identification of an optimal therapeutic approach for fibromyalgic patients, also using tramadol for long periods.

We report two cases of a full-thickness rotator cuff tear followed by acromioclavicular cyst formation in patients with longstanding erosive polyarticular rheumatoid arthritis. One of the consequences of a rotator cuff tear is articular instability with upward migration of the humeral head. The ensuing chronic friction against the undersurface of the acromioclavicular joint caused by arm movements can lead to a non-inflammatory effusion of the acromioclavicular joint with cyst formation. Clinical and ultrasonographic features and a pathogenetic hypothesis are discussed.

Since 1988 to 1992 we analyzed 116,452 consecutive 12-lead electrocardiograms belonging to the entire cohort of 18-year old young boys resident in Padova, Treviso, Rovigo, Venezia, Belluno area (2,834,000 inhabitants). We identified 173 cases of overt WPW pattern (short PR interval, delta wave, anomalous configuration of QRS complex) with a calculated incidence of 1.48/1000. Accessory pathway location was: left free wall (70 patients), right free wall (39 patients), postero-septal (37 patients), antero-septal (15 patients) and undetermined (12 patients). Sixty patients (34.6%) complained of different symptoms as palpitations, near syncope and dizziness. Fifty-three patients (30.6%) went in a regular sport activity. Twenty-four hour Holter monitoring (41 patients) and exercise stress test (43 patients) did not show sustained tachyarrhythmias; intermittent preexcitation was recorded in 23 and 32 patients, respectively. Two-dimensional echocardiogram (68 out of 173) was normal in 44 patients, while 24 showed minor cardiac abnormalities with two major disease; mitral valve prolapse was diagnosed in 8 patients. On the basis of transesophageal (24 patients) or intracardiac (5 patients) electrophysiologic study, 11 patients were considered at high risk for sudden death. Eight of them suffered from spontaneous symptoms.

Following monoaural stimulation, long latency auditory evoked potentials (LLAEPs) recorded from contralateral temporal areas have a shorter latency and larger amplitude than those recorded from the ipsilateral temporal areas. This observation agrees with the operational model drawn up in 1967 by Kimura, which assumes that only anatomically prevailing crossed auditory pathways are active during dichotic hearing, while direct pathways are inhibited. The inputs may then be conveyed to the contralateral cortex, from where they finally reach the ipsilateral temporal areas by means of interhemispheric commissures. It is this mechanism which may underline the right ear advantage for verbal stimuli and the left ear advantage for melodies observed when administering dichotic listening tasks. With the aim of verifying this hypothesis, we recorded temporal LLAEPs in a 21 year-old woman suffering from complex partial seizures, whose CT scan and MRI showed corpus callosum agenesia. Our data support the hypothesis that ipsilateral pathways are greatly inhibited by the contralateral pathways, and therefore auditory stimuli can be supposed to reach the contralateral auditory cortex from where they are transferred through the corpus callosum to the ipsilateral auditory cortex.

The clinical findings of 2 male patients, aged 58 and 60 years with cardiac amyloidosis are described. Congestive heart failure was present in both. Electrocardiograms were abnormal in both cases. Echocardiographic examination showed increased myocardial echogenicity and ventricular hypertrophy, pericardial effusion and decreased ventricular function. Cardiac catheterization was performed in 1 patient. Rectal biopsies were obtained from both patients; endomyocardial biopsy was executed in only 1 patient; all specimens were positive. Our data demonstrate, in agreement with the literature, that clinical features of cardiac amyloidosis are polymorphous and therefore often unidentified.

9 patients with Kaposi's sarcoma, not treated with immunosuppressant drugs, were studied. In the Kaposi's disseminated form an impaired function of T mediated immunity (Leukocytes migration inhibition for PHA and PPD and skin test for DNCB) was found. The number of T lymphocytes (E rosettes) was normal. In the Kaposi's initial form with multiple dermal plaques and nodules, these alterations of cellular immunity were absent. In 4 patients elevated titles of Cytomegalovirus antibodies were found. The occurrence of an impairment of cellular immunity only in the serious and disseminated Kaposi's form is emphasized by the Authors.